Orthodontic treatments of dental malocclusions rely upon influencing the balance between bone formation and bone resorption within the alveolar processes of the maxilla and the mandible. The primary cells involved in the development and metabolism of bone are the osteoblast and the osteoclast. These cells are under the exquisite control of numerous humoral and local factors. Osteocalcin (bone Gla protein, BGP) is one of the predominant proteins in bone, comprising 10-20% of the noncollagenous protein in bone and 1-2% of the total matrix protein. Exclusively synthesized by mature osteoblast cells, osteocalcin is useful as a marker in monitoring osteoblastic activity, bone function and bone metabolism. However, the true biological role of osteocalcin has yet to be determined. The studies proposed in this project are designed to explore the role of osteocalcin in the bone resorptive process. Through various modes of presentation, osteocalcin may interact with osteoclasts and/or their precursors involved in the coupled event of' bone resorption and bone formation. Several laboratories have demonstrated the response of bone resorbing cells and their presumed monocytic precursors to osteocalcin. Osteocalcin has been'-shown to be a chemoattractant for monocytes and embryonic mesenchymal cells. -The precise peptide structure eliciting this chemotactic behavior has been variably reported to be localized at the carboxy-terminus and within the central Gla domain of the protein. The chemoattractant activity for monocytes and mesenchymal cells predicts the presence of a cell surface receptor for osteocalcin. The experimental approach of this project will involve characterization of the osteocalcin receptor in monocytic cells. The studies outlined in this plan will help to define the role played by osteocalcin in regulating bone resorption.